A monoclonal antibody with specificity for hairy cell leukemia cells defines an activation antigen of 60-70 kD present on activated B cells and activated monocytes. This antibody (anti- HC2) inhibits BCGF-induced B-cell proliferation, BCDF activity, and appears to have an indirect mitogenic effect on human peripheral blood B cells. We propose to investigate human B-cell activation with the help of two different monoclonal antibodies (anti-HC2 and BL4) that are both able to inhibit factor activities and which appear to define unique membrance antigens. These studies may identify B-cell lymphokine receptors. Receptors for BCGF and BCDF activities have not yet been described. In particular we will define the mitogenic affect of anti-HC2 on human B cells, investigate the inhibition of BCGF and BCDF activities, and attempt to purify the factor(s) inhibited by anti- HC2. These studies should allow us to identify the natural ligand for the HC2 activation antigen. In addition biochemical studies on the posttranslational modification of the HC2 molecule and amino acid sequence of HC2 are proposed. An amino acid sequence will then allow us to synthesize oligonucleotides and screen cDNA libraries from B lymphoblastoid cell lines expressing the HC2 antigen. An alternative approach using the lambda gtll expression vector is also discussed. The gene for HC2 will thus be cloned and sequenced. This appears to be the most direct approach to the elucidation of the structure and function of the HC2 molecule. Similar studies will be performed simultaneously for the BL4 molecule, which represents another candidate for a B-cell lymphokine receptor.